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Persistent homology

Stephen C West, Ying Wai Chan
The efficient processing of homologous recombination (HR) intermediates, which often contain four-way structures known as Holliday junctions (HJs), is required for proper chromosome segregation at mitosis. Eukaryotic cells possess three distinct pathways of resolution: (i) HJ dissolution mediated by BLM-topoisomerase IIIα-RMI1-RMI2 (BTR) complex, and HJ resolution catalyzed by either (ii) SLX1-SLX4-MUS81-EME1-XPF-ERCC1 (SMX complex) or (iii) GEN1. The BTR pathway acts at all times throughout the cell cycle, whereas the actions of SMX and GEN1 are restrained in S phase and become elevated late in the cell cycle to ensure the resolution of persistent recombination intermediates before mitotic division...
January 18, 2018: Cold Spring Harbor Symposia on Quantitative Biology
Damien Roux, Matthew Schaefers, Bradley S Clark, Molly Weatherholt, Diane Renaud, David Scott, John J LiPuma, Gregory Priebe, Craig Gerard, Deborah R Yoder-Himes
Burkholderia dolosa caused an outbreak in the cystic fibrosis clinic at Boston Children's Hospital and was associated with high mortality in these patients. This species is part of a larger complex of opportunistic pathogens known as the Burkholderia cepacia complex (Bcc). Compared to other species in the Bcc, B. dolosa is highly transmissible; thus understanding its virulence mechanisms is important for preventing future outbreaks. The genome of one of the outbreak strains, AU0158, revealed a homolog of the lafA gene encoding a putative lateral flagellin, which, in other non-Bcc species, is used for movement on solid surfaces, attachment to host cells, or movement inside host cells...
2018: PloS One
Tarsila M Camargo, Rafael N Stipp, Lívia A Alves, Erika N Harth-Chu, José F Höfling, Renata O Mattos-Graner
Streptococcus sanguinis is a pioneer species of teeth and a common opportunistic pathogen of infective endocarditis. In this study, we identified a two-component system, SptRS Ss , affecting S. sanguinis survival in saliva and biofilm formation. Isogenic mutants of sptRSs (SKsptR) and sptSSs (SKsptS) showed reduced cell counts in ex vivo assays of viability in saliva, compared to parent strain SK36 and complemented mutants. Reduced counts of the mutants in saliva were associated with reduced growth rates in poor nutrient medium (RPMI) and increased susceptibility to deposition of C3b and MAC of the complement system, a defense component of saliva and serum...
January 16, 2018: Infection and Immunity
Carolyn A Turcotte, Solomon A Sloat, Julia A Rigothi, Erika Rosenkranse, Alexandra L Northrup, Nicolas P Andrews, Paula M Checchi
Meiotic recombination depends upon the tightly coordinated regulation of chromosome dynamics and is essential for the production of haploid gametes. Central to this process is the formation and repair of meiotic double-stranded breaks (DSBs), which must take place within the constraints of a specialized chromatin architecture. Here, we demonstrate a role for the nucleosome remodeling and deacetylase (NuRD) complex in orchestrating meiotic chromosome dynamics in Caenorhabditis elegans. Our data reveal that the conserved Mi2 homologs Chromodomain helicase DNA binding protein (CHD-3) and its paralog LET-418 facilitate meiotic progression by ensuring faithful repair of DSBs through homologous recombination...
January 16, 2018: Genetics
Kathryn J Sieverman, Jasper Rine
Specialized chromatin domains repress transcription of genes within them and present a barrier to many DNA-protein interactions. Silent chromatin in the budding yeast Saccharomyces cerevisiae, akin to heterochromatin of metazoans and plants, inhibits transcription of PolII- and PolIII-transcribed genes, yet somehow grants access to proteins necessary for DNA transactions like replication and homologous recombination. In this study, we adapted a novel assay to detect even transient changes in the dynamics of transcriptional silencing at HML after it served as a template for homologous recombination...
January 16, 2018: Genetics
Naveen K C Gowda, Jayasankar M Kaimal, Roman Kityk, Chammiran Daniel, Jobst Liebau, Marie Öhman, Matthias P Mayer, Claes Andréasson
Protein quality control depends on the tight regulation of interactions between molecular chaperones and polypeptide substrates. Substrate release from the chaperone Hsp70 is triggered by nucleotide-exchange factors (NEFs) that control folding and degradation fates via poorly understood mechanisms. We found that the armadillo-type NEFs budding yeast Fes1 and its human homolog HspBP1 employ flexible N-terminal release domains (RDs) with substrate-mimicking properties to ensure the efficient release of persistent substrates from Hsp70...
January 2018: Nature Structural & Molecular Biology
Kedi Wu, Guo-Wei Wei
The understanding of toxicity is of paramount importance to human health and environmental protection. Quantitative toxicity analysis has become a new standard in the field. This work introduces element specific persistent homology (ESPH), an algebraic topology approach, for quantitative toxicity prediction. ESPH retains crucial chemical information during the topological abstraction of geometric complexity and provides a representation of small molecules that cannot be obtained by any other method. To investigate the representability and predictive power of ESPH for small molecules, ancillary descriptors have also been developed based on physical models...
January 9, 2018: Journal of Chemical Information and Modeling
Molly C Kottemann, Brooke A Conti, Francis P Lach, Agata Smogorzewska
The protection and efficient restart of stalled replication forks is critical for the maintenance of genome integrity. Here, we identify a regulatory pathway that promotes stalled forks recovery from replication stress. We show that the mammalian replisome component C20orf43/RTF2 (homologous to S. pombe Rtf2) must be removed for fork restart to be optimal. We further show that the proteasomal shuttle proteins DDI1 and DDI2 are required for RTF2 removal from stalled forks. Persistence of RTF2 at stalled forks results in fork restart defects, hyperactivation of the DNA damage signal, accumulation of single-stranded DNA (ssDNA), sensitivity to replication drugs, and chromosome instability...
January 4, 2018: Molecular Cell
Quanxin Long, Ran Yan, Jieli Hu, Dawei Cai, Bidisha Mitra, Elena S Kim, Alexander Marchetti, Hu Zhang, Soujuan Wang, Yuanjie Liu, Ailong Huang, Haitao Guo
Hepadnavirus covalently closed circular (ccc) DNA is the bona fide viral transcription template, which plays a pivotal role in viral infection and persistence. Upon infection, the non-replicative cccDNA is converted from the incoming and de novo synthesized viral genomic relaxed circular (rc) DNA, presumably through employment of the host cell's DNA repair mechanisms in the nucleus. The conversion of rcDNA into cccDNA requires preparation of the extremities at the nick/gap regions of rcDNA for strand ligation...
December 2017: PLoS Pathogens
Francesca Bottacini, Aldert Zomer, Christian Milani, Chiara Ferrario, Gabriele Andrea Lugli, Muireann Egan, Marco Ventura, Douwe van Sinderen
BACKGROUND: Bifidobacterium breve represents a common member of the infant gut microbiota and its presence in the gut has been associated with host well being. For this reason it is relevant to investigate and understand the molecular mechanisms underlying the establishment, persistence and activities of this gut commensal in the host environment. RESULTS: The assessment of vegetative promoters in the bifidobacterial prototype Bifidobacterium breve UCC2003 was performed employing a combination of RNA tiling array analysis and cDNA sequencing...
December 28, 2017: BMC Genomics
Juan Lafuente-Barquero, Sarah Luke-Glaser, Marco Graf, Sonia Silva, Belén Gómez-González, Arianna Lockhart, Michael Lisby, Andrés Aguilera, Brian Luke
RNA-DNA hybrids are naturally occurring obstacles that must be overcome by the DNA replication machinery. In the absence of RNase H enzymes, RNA-DNA hybrids accumulate, resulting in replication stress, DNA damage and compromised genomic integrity. We demonstrate that Mph1, the yeast homolog of Fanconi anemia protein M (FANCM), is required for cell viability in the absence of RNase H enzymes. The integrity of the Mph1 helicase domain is crucial to prevent the accumulation of RNA-DNA hybrids and RNA-DNA hybrid-dependent DNA damage, as determined by Rad52 foci...
December 27, 2017: PLoS Genetics
Allison E James, Artem S Rogovskyy, Michael A Crowley, Troy Bankhead
In Borrelia hermsii, antigenic variation occurs as a result of a nonreciprocal gene conversion event that places one of ~60 silent variable major protein genes downstream of a single, transcriptionally active promoter. The upstream homology sequence (UHS) and downstream homology sequence (DHS) are two putative cis-acting DNA elements that have been predicted to serve as crossover points for homologous recombination. In this report, a targeted deletion/in cis complementation technique was used to directly evaluate the role for these elements in antigenic switching...
December 17, 2017: MicrobiologyOpen
Beatriz Navarro-Domínguez, Francisco J Ruiz-Ruano, Juan Pedro M Camacho, Josefa Cabrero, María Dolores López-León
Parasitic B chromosomes invade and persist in natural populations through several mechanisms for transmission advantage (drive). They may contain gene-derived sequences which, in some cases, are actively transcribed. A further interesting question is whether B-derived transcripts become functional products. In the grasshopper Eyprepocnemis plorans, one of the gene-derived sequences located on the B chromosome shows homology with the gene coding for the CAP-G subunit of condensin I. We show here, by means of fluorescent in situ hybridization coupled with tyramide signal amplification (FISH-TSA), that this gene is located in the distal region of the B24 chromosome variant...
December 15, 2017: Scientific Reports
Leticia Perez, Ushma Patel, Marissa Rivota, Irina E Calin-Jageman, Robert J Calin-Jageman
Most long-term memories are forgotten. What happens, then, to the changes in neuronal gene expression that were initially required to encode and maintain the memory? Here we show that the decay of recall for long-term sensitization memory in Aplysia is accompanied both by a form of savings memory (easier relearning) and by persistent transcriptional regulation. A behavioral experiment (N = 14) shows that sensitization training produces a robust long-term sensitization memory, but that recall fades completely within 1 wk...
January 2018: Learning & Memory
Nurit Haspel, Dong Luo, Eduardo González
BACKGROUND: Understanding protein structure and dynamics is essential for understanding their function. This is a challenging task due to the high complexity of the conformational landscapes of proteins and their rugged energy levels. In particular, it is important to detect highly populated regions which could correspond to intermediate structures or local minima. RESULTS: We present a hierarchical clustering and algebraic topology based method that detects regions of interest in protein conformational space...
December 6, 2017: BMC Bioinformatics
Andrea Nicolussi, Joe Dan Dunn, Georg Mlynek, Marzia Bellei, Marcel Zámocký, Gianantonio Battistuzzi, Kristina Djinovic-Carugo, Paul G Furtmüller, Thierry Soldati, Christian Obinger
Oxidation of halides and thiocyanate by heme peroxidases to antimicrobial oxidants is an important cornerstone in the innate immune system of mammals. Interestingly, phylogenetic and physiological studies suggest that homologous peroxidases are already present in mycetozoan eukaryotes such as Dictyostelium discoideum This social amoeba kills bacteria via phagocytosis for nutrient acquisition at its single-cell stage and for antibacterial defense at its multicellular stages. Here we demonstrate that peroxidase A from D...
December 14, 2017: Journal of Biological Chemistry
Nicholas A Crossland, Xavier Alvarez, Monica E Embers
Non-human primates currently serve as the best experimental model for Lyme disease due to their close genetic homology with humans and demonstration of all three phases of disease following infection with Borreliella (Borrelia) burgdorferi (Bb). We investigated the pathology associated with late disseminated Lyme disease (12 to 13 months following tick inoculation) in doxycycline-treated (28 days; 5mg/kg, oral, 2x/day) and untreated rhesus macaques (Rm). Minimal to moderate lymphoplasmacytic inflammation, with a predilection for perivascular spaces and collagenous tissues, was observed in multiple tissues including the cerebral leptomeninges, brainstem, peripheral nerves from both fore and hind limbs, stifle synovium and perisynovial adipose tissue, urinary bladder, skeletal muscle, myocardium, and visceral pericardium...
December 11, 2017: American Journal of Pathology
Marli Ferreira, Thamires S Moreira, Rodrigo Cristiano, Hugo Gallardo, Ahmed Bentaleb, Pierre Dechambenoit, Elizabeth A Hillard, Fabien Durola, Harald Reinhart Bock
Dibenzo[a,j]coronene-tetracarboxylic alkyl esters and imides with either a centrosymmetric bis-peri substitution pattern or a polar bis-ortho substitution pattern form hexagonal columnar mesophases, which in the case of the imides persist at room temperature. The bis-peri isomers are obtained via a two-fold oxidative photocyclization; the bis-ortho isomers are accessed via a glyoxylic Perkin reaction of triphenylene and naphthalene building blocks. Steric congestion between the substituents and the adjacent benzo protrusion in the bis-ortho esters and imides leads to bending of the aromatic plane, which thus avoids twisting...
December 8, 2017: Chemistry: a European Journal
Arko Sen, Katherine Gurdziel, Jenney Liu, Wen Qu, Oluwademi O Nuga, Rayanne B Burl, Maik Hüttemann, Roger Pique-Regi, Douglas M Ruden
Traumatic brain injury (TBI) can cause persistent pathological alteration of neurons. This may lead to cognitive dysfunction, depression and increased susceptibility to life threatening diseases, such as epilepsy and Alzheimer's disease. To investigate the underlying genetic and molecular basis of TBI, we subjected w1118Drosophila melanogaster to mild closed head trauma and found that mitochondrial activity is reduced in the brains of these flies 24 h after inflicting trauma. To determine the transcriptomic changes after mild TBI, we collected fly heads 24 h after inflicting trauma, and performed RNA-seq analyses...
2017: Frontiers in Genetics
Elizabeth T Barfield, Kyle J Gerber, Kelsey S Zimmermann, Kerry J Ressler, Ryan G Parsons, Shannon L Gourley
In humans and rodents, stress promotes habit-based behaviors that can interfere with action-outcome decision-making. Further, developmental stressor exposure confers long-term habit biases across rodent-primate species. Despite these homologies, mechanisms remain unclear. We first report that exposure to the primary glucocorticoid corticosterone (CORT) in adolescent mice recapitulates multiple neurobehavioral consequences of stressor exposure, including long-lasting biases towards habit-based responding in a food-reinforced operant conditioning task...
November 29, 2017: PLoS Biology
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